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Background: Sudomotor dysfunction is one of the earliest manifestations of small fiber neuropathy (SFN), reflecting the alteration of sympathetic C fiber innervation of the sweat glands. Among other techniques, such innervation can be assessed by measuring electrochemical skin conductance (ESC) in microsiemens (µS). In this study, ESC was measured at the feet to detect distal SFN. For this objective, the performance of a new device, the Body Scan® (Withings, France), intended for home use, was compared with that of a reference device, the Sudoscan® (Impeto Medical, France), which requires a hospital setting. Methods: In patients with diabetes with or without neuropathy or non-diabetic patients with lower-limb neuropathy, the diagnostic performance of the Body Scan® measurement was assessed by calculating its sensitivity (Se) and specificity (Sp) to detect at least moderate SFN (Se70 and Sp70), defined by a value of feet ESC ≤ 70 µS and > 50 µS on the Sudoscan® measure, or severe SFN (Se50 and Sp50), defined by a value of feet ESC ≤ 50 µS on the Sudoscan® measure. The agreement between the two devices was assessed with the analysis of Bland-Altman plots, mean absolute error (MAE), and root mean squared error (RMSE) calculations. The repeatability of the measurements was also compared between the two devices. Results: A total of 147 patients (52% men, mean age 59 years old, 76% diabetic) were included in the analysis. The sensitivity and specificity to detect at least moderate or severe SFN were: Se70 = 0.91 ([0.83, 0.96]), Sp70 = 0.97 ([0.88, 0.99]), Se50 = 0.91 ([0.80, 0.98]), and Sp50 = 0.99 ([0.94, 1]), respectively. The bias and 95% limits of agreement were 1.5 [-5.4, 8.4]. The MAE was 2.9 and the RMSE 3.8. The intra-sample variability was 2.0 for the Body Scan® and 2.3 for the Sudoscan®. Conclusion: The ESC measurements provided by the Body Scan® were in almost perfect agreement with those provided by the reference device, the Sudoscan®, which validates the accuracy of the Body Scan® for the detection of SFN. By enabling simple, rapid, and autonomous use by the patient at home, this new technique will facilitate screening and monitoring of SFN in daily practice. [ABSTRACT FROM AUTHOR]

Summary: Background: No prospective diagnostic studies have directly compared widespread non‐invasive liver tests in patients with type 2 diabetes (T2D) using the intention‐to‐diagnose method for each of the three main histological features of metabolic dysfunction associated steatotic liver disease ‐ namely fibrosis, metabolic dysfunction‐associated steatohepatitis (MASH), and steatosis. Aims: To compare the performance of nine tests using the intention‐to‐diagnose rather than the standard method, which would exclude non‐evaluable participants Methods: Biopsy was used as the reference with predetermined cut‐offs, advanced fibrosis being the main endpoint. The Nash‐FibroTest panel including FibroTest‐T2D, SteatoTest‐T2D and MashTest‐T2D was optimised for type 2 diabetes. FibroTest‐T2D was compared to vibration‐controlled transient elastography stiffness (VCTE), two‐dimensional shear‐wave elastography stiffness (TD‐SWE), and Fibrosis‐4 blood test. NashTest‐T2D was compared to aspartate aminotransferase. SteatoTest‐T2D was compared to the controlled attenuation parameter and the hepatorenal gradient. Results: Among 402 cases, non‐evaluable tests were 6.7% for VCTE, 4.0% for hepatorenal gradient, 3.2% for controlled attenuation parameter, 1.5% for TD‐SWE, 1.2% for NashTest‐T2D, and 0.02% for Fibrosis‐4, aspartate aminotransferase and SteatoTest‐T2D. The VCTE AUROC for advanced fibrosis was over‐estimated by 6% (0.83 [95% CI: 0.78–0.87]) by standard analysis compared to intention‐to‐diagnose (0.77 [0.72–0.81] p = 0.008). The AUROCs for advanced fibrosis did not differ significantly in intention‐to‐diagnose between FibroTest‐T2D (0.77; 95% CI: 0.73–0.82), VCTE (0.77; 95% CI: 0.72–0.81) and TD‐SWE(0.78; 0.74–0.83) but were all higher than the Fibrosis‐4 score (0.70; 95% CI all differences ≥7%; p ≤ 0.03). For MASH, MashTest‐T2D had a higher AUROC (0.76; 95% CI: 0.70–0.80) than aspartate aminotransferase (0.72; 95% CI: 0.66–0.77; p = 0.035). For steatosis, AUROCs did not differ significantly between SteatoTest‐T2D, controlled attenuation parameter and hepatorenal gradient. Conclusions: In intention‐to‐diagnose analysis, FibroTest‐T2D, TD‐SWE and VCTE performed similarly for staging fibrosis, and out‐performed Fibrosis‐4 in outpatients with type 2 diabetes. The standard analysis over‐estimated VCTE performance. ClinicalTrial.gov: NCT03634098. [ABSTRACT FROM AUTHOR]

Summary: Background: One of the unmet needs in patients with type 2 diabetes mellitus (T2DM) is the prediction of non‐alcoholic liver disease by non‐invasive blood tests, for each of the three main histological features, fibrosis, non‐alcoholic steatohepatitis (NASH) and steatosis. Aims: To validate externally the performances of a recent panel, Nash‐FibroTest, for the assessment of the severity of fibrosis stages, NASH grades and steatosis grades. Methods: We prospectively analysed 272 patients with T2DM. Standard definitions of stages and grades were used, and analyses were centralised and blinded. The performances of the FibroTest, NashTest‐2 and SteatoTest‐2 were assessed using the Obuchowski measure (OM), the main outcome recommended as a summary measure of accuracy includeing all pairwise stages and grades comparisons, which is not provided par the extensively used binary area under the ROC curve. Results: The diagnostic performance of each component of the panel was significant. OM (SE; significance) of the FibroTest, the NashTest‐2 and the SteatoTest‐2 was 0.862 (0.012; P < 0.001), 0.827 (0.015; P < 0.001) and 0.794 (0.020; P < 0.01), respectively. For ballooning and lobular inflammation, OM was 0.794 (0.021; P < 0.001) and 0.821 (0.017; P < 0.001), respectively. In a post hoc analysis the FibroTest outperformed VCTE by 4.1% (2.5‐6.5; P < 0.001) for reliability, with a non‐significant difference for OM for fibrosis staging, 0.859 (0.012) for FibroTest vs 0.870 (0.009) for VCTE. Conclusions: From a single blood sample, the panel provides non‐invasive diagnosis of the stages of fibrosis, and the grades of NASH and steatosis in patients with T2DM. Trial registration number: NCT03634098. [ABSTRACT FROM AUTHOR]

A significant number of studies invoked diabetes as a risk factor for virus infections, but the issue remains controversial. We aimed to examine whether non-autoimmune diabetes mellitus enhances the risk of virus infections compared with the risk in healthy individuals without non-autoimmune diabetes mellitus. In this systematic review and meta-analysis, we assessed case-control and cohort studies on the association between non-autoimmune diabetes and viruses. We searched PubMed, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Web of Science with no language restriction, to identify articles published until February 15, 2021. The main outcome assessment was the risk of virus infection in individuals with non-autoimmune diabetes. We used a random-effects model to pool individual studies and assessed heterogeneity (I2) using the χ2 test on Cochrane's Q statistic. This study is registered with PROSPERO, number CRD42019134142. Out of 3136 articles identified, we included 68 articles (90 studies, as the number of virus and or diabetes phenotype varied between included articles). The summary OR between non-autoimmune diabetes and virus infections risk were, 10.8(95% CI: 10.3–11.4; 1-study) for SARS-CoV-2; 3.6(95%CI: 2.7–4.9, I2 = 91.7%; 43-studies) for HCV; 2.7(95% CI: 1.3–5.4, I2 = 89.9%, 8-studies;) for HHV8; 2.1(95% CI: 1.7–2.5; 1-study) for H1N1 virus; 1.6(95% CI: 1.2–2.13, I2 = 98.3%, 27-studies) for HBV; 1.5(95% CI: 1.1–2.0; 1-study) for HSV1; 3.5(95% CI: 0.6–18.3 , I2 = 83.9%, 5-studies) for CMV; 2.9(95% CI: 1–8.7, 1-study) for TTV; 2.6(95% CI: 0.7–9.1, 1-study) for Parvovirus B19; 0.7(95% CI: 0.3–1.5 , 1-study) for coxsackie B virus; and 0.2(95% CI: 0–6.2; 1-study) for HGV. Our findings suggest that, non-autoimmune diabetes is associated with increased susceptibility to viruses especially SARS-CoV-2, HCV, HHV8, H1N1 virus, HBV and HSV1. Thus, these viruses deserve more attention from diabetes health-care providers, researchers, policy makers, and stakeholders for improved detection, overall proper management, and efficient control of viruses in people with non-autoimmune diabetes. [ABSTRACT FROM AUTHOR]

Background To estimate the 10-year incidence of referable diabetic retinopathy (DR) in a French population with type 1 and 2 diabetes mellitus (DM). A secondary objective was the assessment of safe screening intervals in patients with diabetes without retinopathy. Methods Observational, prospective and multicentric study between June 2004 and September 2017 based on a regional screening programme for DR in the Paris region. The incidence of referable DR in patients without retinopathy at baseline was calculated by the Turnbull survival estimator. A safe screening interval was defined as a 95% probability of remaining without referable DR. Results Among the 25 745 participants with type 1 (n=6086) or type 2 (n=19 659) DM, the 10-year cumulative incidence of referable DR was 19.10% (95% CI 17.21% to 21.14%) and 17.03% (15.78% to 18.35%), median (IQR) follow-up= 3.33 (4.24) years. The safe screening interval for patients without DR at the first examination for type 1 and 2 DM was 2.2 (95% CI 2.0 to 2.4) and 3.0 (2.9 to 3.1) years, respectively. In a subgroup of low-risk patients with type 2 DM, the safe screening interval was 4.2 (3.8 to 4.6) years. Conclusions These data suggest that in Paris area, a 2-year, 3-year and 4-year screening interval was considered safe for type 1 DM, type 2 DM and for low-risk patients with type 2 DM, respectively, without DR at the first examination. While these data might be used to support the consideration of extending screening intervals, a randomised clinical trial would be suitable to confirm the safety for patients with DM. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: The objective of this subgroup analysis is to investigate the effectiveness of liraglutide in people with type 2 diabetes (T2D) treated within the primary care physician (PCP) and specialist care settings.Methods: EVIDENCE is a prospective, observational study of 3152 adults with T2D recently starting or about to start liraglutide treatment in France. We followed patients in the PCP and specialist settings for 2 years to evaluate the effectiveness of liraglutide in glycemic control and body weight reduction. Furthermore, we evaluated the changes in combined antihyperglycemic treatments, the reasons for prescribing liraglutide, patient satisfaction, and safety of liraglutide in these two treatment settings.Results: After 2 years of follow-up, 477 out of 1209 (39.0%) of PCP and 297 out of 1398 (21.2%) of specialist-treated patients still used liraglutide and maintained the glycated hemoglobin (HbA1c) target of <7.0%. Significant reductions from baseline were observed in both PCP- and specialist-treated cohorts in mean HbA1c (-1.22% and -0.8%, respectively), fasting plasma glucose (FPG) concentration (-39 and -23 mg/dL), body weight (-4.4 and -3.8 kg), and body mass index (BMI) (-1.5 and -1.4 kg/m2), all p < 0.0001. Reductions in HbA1c and FPG were significantly greater among PCP- compared with specialist-treated patients, p < 0.0001 for both. Patient treatment satisfaction was also significantly increased in both cohorts. Reported gastrointestinal adverse events were less frequent among PCP-treated patients compared with specialist-treated patients (4.5% vs. 16.1%).Conclusion: Despite differences in demography and clinical characteristics of patients treated for T2D in PCP and specialty care, greater reduction in HbA1c and increased glycemic control durability were observed with liraglutide in primary care, compared with specialist care. These data suggest that liraglutide treatment could benefit patients in primary care by delaying the need for further treatment intensification.Trial Registration: ClinicalTrials.gov identifier, NCT01226966.Funding: Novo Nordisk A/S. [ABSTRACT FROM AUTHOR]

Introduction: The extent to which postprandial glucagon reductions contribute to lowering of postprandial glucose in patients with type 2 diabetes mellitus (T2DM) is currently unknown. The aim of this analysis was to determine whether a reduction in postprandial glucagon following treatment with the glucagon-like peptide-1 receptor agonist lixisenatide correlates with a reduction in postprandial glucose and glycated hemoglobin (HbA) in patients with T2DM. Methods: A post hoc analysis was performed on pooled data from the modified intent-to-treat populations of two lixisenatide Phase 3 trials: GetGoal-M (lixisenatide versus placebo as add-on to metformin) and GetGoal-S (lixisenatide versus placebo as add-on to sulfonylurea [SU] ± metformin). Glucagon levels were assessed 2 h after a standardized meal test performed at baseline and Week 24 and were examined for correlation with changes in 2-h postprandial glucose and HbA. Results: Lixisenatide reduced 2-h postprandial glucagon at Week 24 compared with placebo ( P < 0.00001). The mean change in postprandial glucagon significantly correlated with reductions in postprandial glucose ( P < 0.00001) and HbA ( P < 0.00001). Conclusion: A reduction in postprandial glucagon following lixisenatide administration correlated with a decrease in postprandial glucose and HbA in patients with T2DM insufficiently controlled on metformin and/or SU. This suggests that lowering of postprandial glucagon contributes to the overall glycemic improvement observed with lixisenatide. Funding: Sanofi. Clinical Trial Numbers: NCT00712673 (GetGoal-M) and NCT00713830 (GetGoal-S). [ABSTRACT FROM AUTHOR]

Acquired generalized lipodystrophy (AGL) is a rare disease thought to result from autoimmune destruction of adipose tissue. Peripheral T-cell lymphoma (PTCL) has been reported in two AGL patients. We report five additional cases of lymphoma in AGL, and analyze the role of underlying autoimmunity and recombinant human leptin (metreleptin) replacement in lymphoma development. Three patients developed lymphoma during metreleptin treatment (two PTCL and one ALK-positive anaplastic large cell lymphoma), and two developed lymphomas (mycosis fungoides and Burkitt lymphoma) without metreleptin. AGL is associated with high risk for lymphoma, especially PTCL. Autoimmunity likely contributes to this risk. Lymphoma developed with or without metreleptin, suggesting metreleptin does not directly cause lymphoma development; a theoretical role of metreleptin in lymphoma progression remains possible. For most patients with AGL and severe metabolic complications, the proven benefits of metreleptin on metabolic disease will likely outweigh theoretical risks of metreleptin in lymphoma development or progression. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to investigate whether the efficacy of liraglutide observed in randomized controlled trials translates into therapeutic benefits in the French population during routine clinical practice.Methods: This observational, prospective, multicenter study included 3152 adults with type 2 diabetes who had recently started or were about to start liraglutide treatment. During 2 years of follow-up, an evaluation of the reasons for prescribing liraglutide, maintenance dose of liraglutide, changes in combined antidiabetic treatments, level of glycemic control, change in body weight and body mass index (BMI), patient satisfaction with diabetes treatment and safety of liraglutide were investigated. The primary study endpoint was the proportion of patients still receiving liraglutide and presenting with HbA1c <7.0% after 2 years of follow-up.Results: At the end of the study, 29.5% of patients maintained liraglutide treatment and reached the HbA(1c) target. Mean (±SD) HbA(1c), fasting plasma glucose concentration, body weight and BMI were significantly reduced from baseline [8.46% (±1.46) to 7.44% (±1.20); 180 (±60) to 146 (±44) mg/dL; 95.2 (±20.0) to 91.1 (±19.6) kg; 34.0 (±7.2) to 32.5 (±6.9) kg/m(2); respectively, all P < 0.0001]. Patient treatment satisfaction increased, with the mean diabetes treatment satisfaction questionnaire status version score increasing from 22.17 (±7.64) to 28.55 (±5.79), P < 0.0001. The main adverse event type was gastrointestinal, with a frequency of 10.9%, and the percentage of patients suffering ≥1 hypoglycemic episode decreased from 6.9% to 4.4%.Conclusion: The results of the EVIDENCE study suggest that the effectiveness of liraglutide in real-world clinical practice is similar to that observed in randomized controlled trials.Funding: Novo Nordisk A/S.Trial Registration: ClinicalTrials.gov identifier, NCT01226966. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To evaluate day-to-day variations of insulin needs in type 2 diabetic patients with end-stage renal disease (ESRD) on maintenance hemodialysis. RESEARCH DESIGN AND METHODS -- We developed a 24-h euglycemic clamp in patients who received an average of 2,200 calories in a standardized three-meal and two-snack regimen per day, adjusted to body size and sex. Intravenous insulin was adjusted every 30 min to achieve 5.5 ± 1.1 mmol/l glycemia over 24 h prehemodialysis, during hemodialysis session, and 24 h posthemodialysis in 10 type 2 diabetic patients, aged 55.7 ± 8.7 years with 11.9 ± 4.5 years diabetes duration, undergoing maintenance hemodialysis for 2.3 ± 2.3 years. Insulin requirements were derived from the dose of insulin administered to maintain euglycemia per period of time and day-to-day comparisons performed. RESULTS -- Mean capillary glycemia was 5.5 ± 0.3 mmol/l prehemodialysis and 5.3 ± 0.2 mmol/l posthemodialysis (P = 0.39). Pre- and posthemodialysis areas under the glucose curve were comparable. This was achieved by infusing 23.6 ± 7.7 IU/24 h prehemodialysis vs. 19.9 ± 4.9 IU/24 h posthemodialysis, indicating a 15.3% decrease posthemodialysis (P = 0.09). Basal insulin needs decreased from 0.4 ± 0.1/h prehemodialysis to 0.3 ± 0.1/h posthemodialysis (P = 0.01). Total boluses were decreased by 2.2 ± 3.1 IU (P =0.15). Changes in blood urea did not correlate with changes in insulin needs (r = 0.1, P = 0.79). CONCLUSIONS--The present study has demonstrated a significant 25% reduction in basal insulin requirements the day after dialysis compared with the day before. No significant change in boluses was observed, and overall the reduction of total insulin requirements was -15% equivalent to -4 IU/day posthemodialysis of marginal statistical significance. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Heterozygous mutations in the human preproinsulin (INS) gene are a cause of nonsyndromic neonatal or early-infancy diabetes. Here, we sought to identify INS mutations associated with maturity-onset diabetes of the young (MODY) or nonautoimmune diabetes in mid-adult life, and to explore the molecular mechanisms involved. RESEARCH DESIGN AND METHODS--The INS gene was sequenced in 16 French probands with unexplained MODY, 95 patients with nonautoimmune early-onset diabetes (diagnosed at <35 years) and 292 normoglycemic control subjects of French origin. Three identified insulin mutants were generated by site-directed mutagenesis of cDNA encoding a preproinsulin--green fluorescent protein (GFP) (C-peptide) chimera. Intracellular targeting was assessed in clonal β-cells by immunocytochemistry and proinsulin secretion, by radioimmunoassay. Spliced XBP1 and C/EBP homologous protein were quantitated by real-time PCR. RESULTS--A novel coding mutation, L30M, potentially affecting insulin multimerization, was identified in five diabetic individuals (diabetes onset 17-36 years) in a single family. L30M preproinsulin-GFP fluorescence largely associated with the endoplasmic reticulum (ER) in MIN6 β-cells, and ER exit was inhibited by ∼50%. Two additional mutants, R55C (at the B/C junction) and R6H (in the signal peptide), were normally targeted to secretory granules, but nonetheless caused substantial ER stress. CONCLUSIONS--We describe three INS mutations cosegregating with early-onset diabetes whose clinical presentation is compatible with MODY. These led to the production of (pre)proinsulin molecules with markedly different trafficking properties and effects on ER stress, demonstrating a range of molecular defects in the β-cell. Diabetes 59:653-661, 2010 [ABSTRACT FROM AUTHOR]

OBJECTIVE--The clinical expression of maturity-onset diabetes of the young (MODY)-3 is highly variable. This may be due to environmental and/or genetic factors, including molecular characteristics of the hepatocyte nuclear factor 1-α (HNF1A) gene mutation. RESEARCH DESIGN AND METHODS--We analyzed the mutations identified in 356 unrelated MODY3 patients, including 118 novel mutations, and searched for correlations between the genotype and age at diagnosis of diabetes. RESULTS--Missense mutations prevailed in the dimerization and DNA-binding domains (74%), while truncating mutations were predominant in the transactivation domain (62%). The majority (83%) of the mutations were located in exons 1- 6, thus affecting the three HNF1A isoforms. Age at diagnosis of diabetes was lower in patients with truncating mutations than in those with missense mutations (18 vs. 22 years, P = 0.005). Missense mutations affecting the dimerization/DNA-binding domains were associated with a lower age at diagnosis than those affecting the transactivation domain (20 vs. 30 years, P = 10-4). Patients with missense mutations affecting the three isoforms were younger at diagnosis than those with missense mutations involving one or two isoforms (P = 0.03). CONCLUSIONS--These data show that part of the variability of the clinical expression in MODY3 patients may be explained by the type and the location of HNF1A mutations. These findings should be considered in studies for the search of additional modifier genetic factors. Diabetes 57:503-508, 2008 [ABSTRACT FROM AUTHOR]

The offspring of Pima Indians with early onset type 2 diabetes are at high risk for developing diabetes at an early age. This risk is greater among those whose mothers were diabetic during pregnancy. To define the metabolic abnormalities predisposing individuals in these high-risk groups to diabetes, we conducted a series of studies to measure insulin secretion and insulin action in healthy adult Pima Indians. In 104 normal glucose-tolerant subjects, acute insulin secretory response (AIR) to a 25-g intravenous glucose challenge correlated with the age at onset of diabetes in the mother (r = 0.23, P = 0.03) and, in multiple regression analyses, the age at onset of diabetes in the father (P = 0.02), after adjusting for maternal age at onset and after allowing for an interaction between these terms. In contrast, insulin action (hyperinsulinemic glucose clamp) did not correlate with the age at onset of diabetes in the parents. To determine whether early onset diabetes in the parents affected insulin secretion in the offspring across a range of glucose concentrations, responses to a stepped glucose infusion were measured in 23 subjects. Insulin secretion rates were lower in individuals whose mothers had developed diabetes before 35 years of age (n = 8) compared with those whose parents remained nondiabetic until at least 49 years of age (n = 15) (average insulin secretory rates: geometric mean [95% CI] 369 [209-652] vs. 571 [418-780] pmol/min, P = 0.007). Finally, the AIR was lower in individuals whose mothers were diabetic during pregnancy (n = 8) than in those whose mothers developed diabetes at an early age but after the birth of the subject (n = 41) (740 [510-1,310] vs. 1,255 [1,045-1,505] pmol/l, P < 0.02). Thus, insulin secretion is lower in normal glucose tolerant offspring of people with early onset type 2 diabetes. This impairment may be worsened by exposure to a diabetic environment in utero. [ABSTRACT FROM AUTHOR]

Knowledge of how the brain contributes to the regulation of food intake in humans is limited. We used positron emission tomography and measures of regional cerebral blood flow (rCBF) (a marker of neuronal activity) to describe the functional anatomy of satiation (i.e., the response to a liquid meal) in the context of extreme hunger (36-h fast) in 11 obese (BMI > or =35 kg/m2, age 27+/-5 years, weight 115+/-11 kg, 38+/-7% body fat; mean +/- SD) and 11 lean (BMI < or =25 kg/m2, age 35+/-8 years, weight 73+/-9 kg, 19+/-6% body fat) men. As in lean men, satiation in obese men produced significant increases in rCBF in the vicinity of the ventromedial and dorsolateral prefrontal cortex and significant decreases in rCBF in the vicinity of the limbic/paralimbic areas (i.e., hippocampal formation, temporal pole), striatum (i.e., caudate, putamen), precuneus, and cerebellum. However, rCBF increases in the prefrontal cortex were significantly greater in obese men than in lean men (P < 0.005). rCBF decreases in limbic/paralimbic areas, temporal and occipital cortex, and cerebellum were also significantly greater in obese men than in lean men (P < 0.005), whereas rCBF decreases in the hypothalamus and thalamus were attenuated in obese men compared with lean men (P < 0.05). This study raises the possibility that the brain responses to a meal in the prefrontal areas (which may be involved in the inhibition of inappropriate response tendencies) and limbic/paralimbic areas (commonly associated with the regulation of emotion) may be different in obese and lean men. Additional studies are required to investigate how these differential responses are related to the pathophysiology of obesity. [ABSTRACT FROM AUTHOR]

Explores regions of the brain that were preferentially affected during the taste perception of a liquid meal in right-handed, fasting men. Areas of the brain with increased regional cerebral blood flow after taste perception; Use of positron emission tomography to assess preferential blood flow.

Presents information on a study which investigated the regions of the human brain that are preferentially affected during hunger and satiation using positron emission tomography measurements. Materials and methods; Results and discussion.

Therapeutic footwear (TFW) is essential to prevent diabetic foot ulcer (DFU) relapse after healing. Our retrospective study aimed at investigating patient's compliance with TFW 1 year after complete healing, and whether the respect of this TFW in real life conditions was associated with a decrease of DFU recurrence during a 1-year follow-up. This is a retrospective study in which all consecutive patients attending our ambulatory foot unit between 01.2015 and 01.2016, were included if they had a TFW prescription after complete healing. The primary study endpoint was the percentage of compliant patients, who wear the TFW at 1 year. The proportion of patient with DFU relapse was compared in compliant versus non-compliant patients (secondary endpoint). The use of TFW was assessed by analyzing the points of wear and cleanliness of the shoes by the same podiatrist. We included 117 consecutive patients: age 63 ± 13 years, women 29/117 (24,7%), type 2 diabetes: 108/117 (92%), diabetes duration: 17.5 ± 12.5 years. After 12 months, 28/117 patients (24%) were lost of follow-up. TFW was respected in 60/117 cases (51.2%). None of these factors influenced the TFW compliance: sex, age, type of diabetes, diabetic treatment, diabetic duration or complications, HbA1c level, peripheral artery disease, neuropathy, amputations, ulcer localization, healing time, TFW type nor the lack of social insurance. DFU recurrence was observed in 24/89 cases (27%) and was significantly higher in non-compliant patients: 16/29 (55%) vs. 8/60 (13.3%) (P=0.05). The only factor predictive of DFU relapse was non-compliance for TFW. After complete DFU healing, TFW prescription is respected only by half of the patients at 1 year. Non-compliant patients are at higher risk of DFU. Further surveys need to be designed to determine the reasons of non-compliance and to conceive more adapted educational programs. Disclosure: M. Laloi-Michelin: None. T. Vidal-Trécan: Board Member; Self; Novo Nordisk Inc. F. Féron: None. J. Kevorkian: None. D. Acker: None. C. Bouche: None. J. Gautier: None. J. Riveline: Board Member; Self; Abbott, Lilly Diabetes, Novo Nordisk Inc. Consultant; Self; Novo Nordisk Inc. Research Support; Self; Air Liquide, Amgen Inc. Speaker's Bureau; Self; Abbott, Lilly Diabetes, Sanofi. [ABSTRACT FROM AUTHOR]

Background: Bedside Blind Bone Biopsy (B4) performed by a diabetologist has been recently shown as a reliable tool to manage antibiotherapy in case of Diabetic Foot Ulcer (DFU) with suspected osteitis. Here, we evaluated the performance of B4 compared to the conventional procedure (Basic Bone Biopsy, B3) performed either by surgery or interventional radiology. Method: A bicentric, observational, retrospective study was conducted in two different diabetes departments. B4 was performed by a diabetologist from December 2015 to August 2018 (32 months) in Center A. B3 was performed by a surgeon or an interventional radiologist from September 2013 to august 2018 (61 months) in Center B. The primary end point was complete healing with Exclusive Medical Treatment (EMT: offloading, wound care±antibiotherapy) at 3 months. The secondary end points were the rates of contaminations and sterile Bone Biopsies (BB). Results: Among 1112 patients with diabetes mellitus (DM) admitted with foot ulcer, 146 consecutive patients (13%) were presented with clinically and/or radiological suspicion of osteitis and consequently with an indication of BB. B4=97/415 DFU (23%), B3=49/697 DFU (7%, surgery n=33/49 [67.4%], radiology n=16/49 [32.6%]). Patients characteristics were as followed and similar between the 2 groups: males (74.7%), mean age (68.6±12.2 years), mean duration of DM (18.4±10,9 years), mean glycated hemoglobin (8.1±2,1%). No statistical difference was observed for mean delay between time of BB decision and procedure (B4 16.2±13,3 days, B3 13.6±9,3 days, p=0.65), contaminations (B4 10%, B3 10.4%, p=0.86) and sterile BB (B4 36%, B3 22.9%, p=0.10). The rate of patients with complete healing with EMT at 3 months was similar between the two groups (B4 44.8%, B3 28.6%, p=0.12). Conclusion: B4 is a simple and valid diagnostic procedure to manage DFU with suspected osteitis. It results to comparable healing rate than more sophisticated and expensive procedures. Disclosure: F. Féron: None. L. Potier: Advisory Panel; Self; Merck Sharp & Dohme Corp. Consultant; Self; Sanofi. G. Péan de Ponfilly: None. D. Gauthier: None. A. Munier: None. E. Lecorche: None. N. Grall: None. M. Laloi-Michelin: None. F. Mercier: None. T. Vidal-Trécan: Board Member; Self; Novo Nordisk Inc. M. Marre: Advisory Panel; Self; Servier. Board Member; Self; Merck Sharp & Dohme Corp., Novo Nordisk A/S. J. Riveline: Board Member; Self; Abbott, Lilly Diabetes, Novo Nordisk Inc. Consultant; Self; Novo Nordisk Inc. Research Support; Self; Air Liquide, Amgen Inc. Speaker's Bureau; Self; Abbott, Lilly Diabetes, Sanofi. J. Gautier: None. R. Roussel: Advisory Panel; Self; Merck Sharp & Dohme Corp., Sanofi. Consultant; Self; Abbott, AstraZeneca, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Physiogenex. Research Support; Self; Janssen Pharmaceuticals, Inc. J. Kevorkian: None. [ABSTRACT FROM AUTHOR]

Background and Aims: Hypoglycemia is a major threat of insulin therapy, but only severe events are often considered as valid endpoints. Surrogates are required; mild events are logical candidates. The International Hypoglycemia Study Group (IHSG) proposed thresholds (3.9 and 3.0 mmol/L) for representative mild events, but evidence is scarce. Materials and Methods: We studied the correlation of the rate (or the incidence) of non-severe events with the rate (or the incidence) of severe events in a study-level systematic analysis of published data (1/1/00-6/1/18) in insulin-treated patients. Mild event was defined as either "any hypoglycemia," or "severe or confirmed <3.9 mmol/L," or "severe or confirmed <3.0," with a tolerance of +/-0.4 mmol/L to manage the multiplicity of definitions. Nocturnal period was defined as per study design, therefore not homogeneously. Severe events were mostly defined as per IHSG. Results and Conclusion: 127 out of 15570 studies were eventually included. Pearson R² are presented (Figure). The mild hypoglycemia were usually better correlated with incidence rather than rate of severe events. Incidence of severe or confirmed <3.0 mmol/L, especially if limited to the night, appeared to be the best surrogate for incidence of severe events. Disclosure: R. Roussel: Advisory Panel; Self; Merck Sharp & Dohme Corp., Sanofi. Consultant; Self; Abbott, AstraZeneca, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Physiogenex. Research Support; Self; Janssen Pharmaceuticals, Inc. A. Moutairou: None. J. Riveline: Board Member; Self; Abbott, Lilly Diabetes, Novo Nordisk Inc. Consultant; Self; Novo Nordisk Inc. Research Support; Self; Air Liquide, Amgen Inc. Speaker's Bureau; Self; Abbott, Lilly Diabetes, Sanofi. J. Gautier: None. L. Potier: Advisory Panel; Self; Merck Sharp & Dohme Corp. Consultant; Self; Sanofi. Funding: Sanofi [ABSTRACT FROM AUTHOR]

A response by Henri Boulanger, Rafik Mansouri et al to a letter to the editor about their article on the role of peroxisome proliferators-activated receptors (PPAR) agonists in diabetic nephropathy is presented.